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Aloe-emodin induces cell death through S-phase arrest and caspase-dependent pathways in human tongue squamous cancer SCC-4 cells.

Abstract
Aloe-emodin, one of the anthraquinones, has been shown to have anticancer activity in different kinds of human cancer cell lines. Therefore, the purpose of this study was to investigate the anti-cancer effect of aloe-emodin on human tongue squamous carcinoma SCC-4 cells. The results indicated that aloe-emodin induced cell death through S-phase arrest and apoptosis in a dose- and time-dependent manner. Treatment with 30 microM of aloe-emodin led to S-phase arrest through promoted p53, p21 and p27, but inhibited cyclin A, E, thymidylate synthase and Cdc25A levels. Aloe-emodin promoted the release of apoptosis-inducing factor (AIF), endonuclease G (Endo G), pro-caspase-9 and cytochrome c from the mitochondria via a loss of the mitochondrial membrane potential (DeltaPsi(m)) which was associated with a increase in the ratio of B-cell lymphoma 2-associated X protein (Bax)/B cell lymphoma/leukemia-2 (Bcl-2) and activation of caspase-9 and -3. The free radical scavenger N-acetylcysteine (NAC) and caspase inhibitors markedly blocked aloe-emodin-induced apoptosis. Aloe-emodin thus induced apoptosis in the SCC-4 cells through the Fas/death-receptor, mitochondria and caspase cascade. Aloe-emodin could be a novel chemotherapeutic drug candidate for the treatment of human tongue squamous cancer in the future.
AuthorsTsan-Hung Chiu, Wan-Wen Lai, Te-Chun Hsia, Jai-Sing Yang, Tung-Yuan Lai, Ping-Ping Wu, Chia-Yu Ma, Chin-Chung Yeh, Chin-Chin Ho, Hsu-Feng Lu, W Gibson Wood, Jing-Gung Chung
JournalAnticancer research (Anticancer Res) Vol. 29 Issue 11 Pg. 4503-11 (Nov 2009) ISSN: 1791-7530 [Electronic] Greece
PMID20032398 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Anthraquinones
  • Antineoplastic Agents
  • Isoenzymes
  • Reactive Oxygen Species
  • aloe emodin
  • Endodeoxyribonucleases
  • endonuclease G
  • Caspases
  • Calcium
Topics
  • Anthraquinones (pharmacology)
  • Antineoplastic Agents (pharmacology)
  • Apoptosis (drug effects)
  • Calcium (metabolism)
  • Carcinoma, Squamous Cell (drug therapy, metabolism, pathology)
  • Caspases (metabolism)
  • Cell Line, Tumor
  • Endodeoxyribonucleases (metabolism)
  • Humans
  • Isoenzymes (metabolism)
  • Membrane Potential, Mitochondrial (drug effects)
  • Mitochondria (drug effects, enzymology)
  • Reactive Oxygen Species (metabolism)
  • S Phase (drug effects)
  • Tongue Neoplasms (drug therapy, metabolism, pathology)

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